The focus of this proposal is to understand the immune response to pyogenic bacteria, such as S. aureus, in the pathogenesis of experimental brain abscess. This study may lead to identification of host and bacterial factors that play a key role in brain abscess development and pathology. First, they will evaluate, using S. aureus (one of the main etiological agents of brain abscess in humans,) the host immune responses in the central nervous system (CNS) parenchyma. They will use a rodent experimental model, and examine cytokines and chemokines elicited in response to bacterial challenge, the cellular origin(s) of these mediators within the CNS, and the response of primary astrocytes and microglia. Next, they will evaluate the relation of bacterial virulence factors in abscess pathogenesis. They will evaluate the role of virulence factors expressed in the CNS and what effect they have on the host immune response to infection.